Targeting post-translational modifications: novel insights into bone metabolic diseases

Bone metabolic diseases constitute a group of disorders characterized by abnormal alterations in bone mass and skeletal metabolism, often resulting from oxidative stress, nutritional deficiencies, and various other etiological factors. Post-translational modification (PTM), a critical mechanism of protein regulation, plays a pivotal role in the pathogenesis of bone metabolic diseases. While previous reviews have primarily focused on the individual regulatory functions of common PTMs, such as phosphorylation, methylation, and ubiquitination, they have largely overlooked the dynamic interactions and cross talk among different PTMs. In recent years, an increasing number of novel PTMs have been implicated in the progression of bone metabolic diseases; however, comprehensive analyses of their underlying mechanisms and interrelationships remain limited. Therefore, a systematic and updated review of the roles and interplay of PTMs in bone metabolic diseases is warranted.

This review systematically introduced the basic processes of different types of PTMs, including phosphorylation, methylation, ubiquitination, glycosylation, acetylation, SUMOylation, succinylation, palmitoylation, lactylation, ADP-ribosylation, sulfhydration, carbonylation, hydroxylation, citrullination, and farnesylation, and summarized underlying mechanisms and cross talks among these PTMs in regulating the development of bone metabolic diseases.

This review focuses on three key concepts. First, it highlights PTMs that have been implicated in the pathological process of bone metabolic diseases. Second, it examines the regulatory mechanisms and cross talks among different PTMs in bone metabolic diseases. Third, it discusses how aberrant PTMs can disrupt bone metabolic homeostasis by regulating various signaling pathways, leading to cellular dysfunction involved in the onset and development of osteoarthritis, osteoporosis, osteosarcoma, and rheumatoid arthritis. Therefore, an in-depth study of the PTM mechanisms in bone metabolic diseases may facilitate the identification of novel regulatory targets and provide a theoretical foundation for the development of more effective therapeutic strategies.